Attention Deficit Hyperactivity Disorder (ADHD) occurs in 3-6 percent of school-age children and is characterized by inattentiveness, hyperactivity, and impulsivity. Because these symptoms are alleviated by drugs that act on dopaminergic neurons, and because imaging studies implicate brain regions rich in dopamine (DA), current hypotheses of ADHD focus on this neurotransmitter. Although this disorder may have more than one etiology, genetic factors have been implicated in several studies. The present application proposes research that focuses on the genetic influences on ADHD, with particular emphasis on genes that encode proteins known to be important for normal dopaminergic neurotransmission. The fruitfulness of this approach is exemplified by our recent discovery that the distribution of alleles of the polymorphic gene DRD4 (encoding the D4 type of dopamine receptor) differs significantly between ADHD children and controls. The specific aim of the present project is to identify genetic factors in ADHD by applying Haplotype Relative Risk (HRR) analysis to a carefully studied and diagnosed group of probands and their biological parents, and focusing on DA-related genes that are known to have variant forms within the human population. HRR is an innovative technique that avoids major problems in genetic association studies that are caused by differences in allele frequencies between control and experimental samples. We will specifically test the hypothesis that gene variants expected to result in hypodopaminergic activity will be associated with ADHD. These specific aims are designed to subserve the long-term goal of elucidating the biological bases of ADHD.